Optical diagnosis using measurement sequence

ABSTRACT

Devices, systems, and methods that facilitate optical analysis, particularly for the diagnosis and treatment of refractive errors of the eye. An optical diagnostic method for an eye includes obtaining a sequence of aberration measurements of the eye, identifying an outlier aberration measurement of the sequence of aberration measurements, and excluding the outlier aberration measurement from the sequence of aberration measurements to produce a qualified sequence of aberration measurements. The sequence of aberrations measurements can be obtained by using a wavefront sensor. An optical correction for the eye can be formulated in response to the qualified sequence of aberration measurements.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation application under 35 USC § 120 ofU.S. patent application Ser. No. 12/909,756, filed Oct. 21, 2010, whichclaims the benefit of U.S. Provisional Application No. 61/289,324, filedDec. 22, 2009, the entire disclosures of the above two applications arehereby incorporated herein by reference.

BACKGROUND

The present application relates generally to optical diagnosis usingaberration measurements, and relates more particularly to the use of oneor more sequences of aberration measurements to produce an opticaldiagnosis. In many embodiments, a sequence of aberrations measurementsare obtained and used to quantify the aberrations of an eye. Thequantified aberrations are then used to produce an optical diagnosis forthe eye.

Known laser eye procedures generally employ an ultraviolet or infraredlaser to remove a microscopic layer of stromal tissue from the cornea ofthe eye to alter the refractive characteristics of the eye. The laserremoves a selected shape of the corneal tissue, often to correctrefractive errors of the eye. Ultraviolet laser ablation results inphoto-decomposition of the corneal tissue, but generally does not causesignificant thermal damage to adjacent and underlying tissues of theeye. The irradiated molecules are broken into smaller volatile fragmentsphotochemically, directly breaking the intermolecular bonds.

Laser ablation procedures can remove the targeted stroma of the corneato change the cornea's contour for varying purposes, such as forcorrecting myopia, hyperopia, astigmatism, and the like. Control overthe distribution of ablation energy across the cornea may be provided bya variety of systems and methods, including the use of ablatable masks,fixed and moveable apertures, controlled scanning systems, eye movementtracking mechanisms, and the like. In known systems, the laser beamoften comprises a series of discrete pulses of laser light energy, withthe total shape and amount of tissue removed being determined by theshape, size, location, and/or number of a pattern of laser energy pulsesimpinging on the cornea. A variety of algorithms may be used tocalculate the pattern of laser pulses used to reshape the cornea so asto correct a refractive error of the eye. Known systems make use of avariety of forms of lasers and/or laser energy to effect the correction,including infrared lasers, ultraviolet lasers, femtosecond lasers,frequency multiplied solid-state lasers, and the like. Alternativevision correction techniques make use of radial incisions in the cornea,intraocular lenses, removable corneal support structures, thermalshaping, and the like.

Known corneal correction treatment methods have generally beensuccessful in correcting standard vision errors, such as myopia,hyperopia, astigmatism, and the like. However, as with all successes,still further improvements would be desirable. Toward that end,wavefront measurement instruments are now available to measure therefractive characteristics of a particular patient's eye.

One promising wavefront measurement system is the iDESIGN ADVANCEDWAVESCAN STUDIO System, which includes a Hartmann-Shack wavefront sensorassembly that may quantify higher-order aberrations throughout theentire optical system, including first and second-ordersphero-cylindrical errors and third through sixth-order aberrationscaused by coma and spherical aberrations. With advanced algorithms formeasuring and applying the wavefront correction (e.g. Fourier or zonal),even higher spatial frequency structures can be corrected, providingthat adequate registration can be maintained between the intendedcorrection and its application in a practical system. The wavefrontmeasurement of the eye creates a high order aberration map that permitsassessment of aberrations throughout the optical pathway of the eye,e.g., both internal aberrations and aberrations on the corneal surface.Thereafter, the wavefront aberration information may be saved andthereafter input into a computer system to compute a custom ablationpattern to correct the aberrations in the patient's eye. A variety ofalternative wavefront or other aberration measurement systems may alsobe available

Customized refractive corrections of the eye may take a variety ofdifferent forms. For example, lenses may be implanted into the eye, withthe lenses being customized to correct refractive errors of a particularpatient. By customizing an ablation pattern or other refractiveprescription based on wavefront measurements, it may be possible tocorrect minor refractive errors so as to reliably provide visualacuities better than 20/20. Alternatively, it may be desirable tocorrect aberrations of the eye that reduce visual acuity, even where thecorrected acuity remains less than 20/20.

The determination of a customized refractive correction for an eye maybe complicated by the often dynamic nature of the refraction of an eye.The optical aberrations of an eye can vary with, for example, changes inviewing conditions such as viewing distance and/or illumination. Changesin aberrations due to changes in viewing distance can become especiallysignificant as a person ages and presbyopia sets in. Even for viewingdistances within an accommodation range of an eye, differentaccommodation levels have different levels of muscular contraction,which may result in different aberrations due to, for example, changesin the shape of the eye arising from different internal strain levels inthe eye. Even changes in the moisture level of the eye (e.g., tear film)can produce changes in the aberrations of the eye.

Consequently, multiple aberration measurements may be required toaccurately characterize the aberrations of an eye. Thus, improvedmethods and systems that use one or more sequences of aberrationmeasurements to accurately characterize the aberrations of an eye aredesirable. Likewise, improved methods and systems for determining acustomized refractive correction for an eye are also desirable.

BRIEF SUMMARY

The following presents a simplified summary of some embodiments of theinvention in order to provide a basic understanding of the invention.This summary is not an extensive overview of the invention. It is notintended to identify key/critical elements of the invention or todelineate the scope of the invention. Its sole purpose is to presentsome embodiments of the invention in a simplified form as a prelude tothe more detailed description that is presented below.

Improved diagnostic methods and systems are provided. In manyembodiments, one or more sequences of aberrations measurements areobtained using one or more viewing conditions. The aberrationmeasurements can be registered to a common reference. Outliermeasurements can be identified and excluded from consideration. Byexcluding outlier measurements, a resulting optical diagnosis may moreaccurately address non-transient aberrations of the eye withoutintroducing diagnosis errors associated with transient aberrationmeasurements. The outlier measurements can be identified by processing asequence of aberration measurements and/or by processing one or morecorresponding sequences of component aberrations of the eye.

In many embodiments, statistically-significant component aberrations ofthe eye are determined by analyzing a sequence of aberrationsmeasurements. Each aberration measurement of the sequence can be used todetermine component aberrations that, when combined, approximate thecombined aberrations of the eye for that measurement. Each of theresulting series of component aberrations can be analyzed to quantifyhow any particular component aberration changes over time. In manyembodiments, the eye is subjected to different viewing conditions duringthe sequence of aberration measurements so that the effect of thedifferent viewing conditions on the component aberrations can bedetermined. The determination of how the component aberrations changeover time, and change with respect to different viewing conditions,provides data that can be used to select an optical correction for theeye. In many embodiments, one or more candidate optical corrections areevaluated relative to different viewing conditions so as to aid in theselection of an optical correction for the eye.

Thus, in a first aspect, an optical diagnostic method is provided for aneye having a pupil. The method includes obtaining a sequence ofaberration measurements of the eye, identifying an outlier aberrationmeasurement of the sequence of aberration measurements, and excludingthe outlier aberration measurement from the sequence of measurements toproduce a qualified sequence of aberration measurements. In manyembodiments, the sequence of aberration measurements is obtained byusing a wavefront sensor. The qualified sequence of aberrationmeasurements can be used to formulate an optical correction for the eye.

In many embodiments, the sequence of aberration measurements and/or thequalified sequence of aberration measurements are registered by using alocation of the eye. For example, the method can include determining arelationship between a size of the pupil and a location of the pupil,determining a plurality of sizes of the pupil corresponding to thesequence of aberration measurements, and registering the sequence ofaberration measurements with a location of the eye by using theplurality of pupil sizes and the relationship.

In many embodiments, the sequence of aberration measurements and/or thequalified sequence of measurements are registered with an orientation ofthe eye (e.g., rotation about an optical axis of the eye). For example,the method can include measuring a plurality of orientations of the eyecorresponding to the sequence of aberration measurements. And theaberration measurements can be registered with an orientation of the eyeby using the measured orientations. The orientations of the eye can bemeasured, for example, by measuring a position of at least one of anatural feature of the eye (e.g., limbus, blood vessel(s) on the sclera,edge of iris) or an artificial reference mark added to the eye (e.g., aphysical mark placed on the sclera).

The method can include identifying statistically-significant componentaberrations of the eye. For example, the method can include determininga sequence of coefficients corresponding to a component aberration ofthe eye in response to at least one of the sequence of aberrationmeasurements or the qualified sequence of aberration measurements, andprocessing the sequence of coefficients to determine whether thecomponent aberration is statistically significant.

Identifying an outlier aberration measurement can be accomplished invarious ways. For example, a sequence of coefficients corresponding to acomponent aberration of the eye can be processed to identify an outlieraberration measurement by, for example, detecting one or morecoefficients of the sequence that deviate significantly from theprevailing trend of the sequence of coefficients. Post-blink aberrationmeasurements that follow a blink of the eye by less than a predeterminedamount of time can be identified as outlier measurements and can then beexcluded or considered for exclusion. Identifying a blink can include atleast one of detecting a radius of the pupil that is less than apredetermined value, detecting a rate of change of the pupil that isgreater that a predetermined rate, or detecting a radius of the pupilthat is inconsistent with a linear interpolation based on nearbyqualified radius measurements of the pupil. An outlier measurement canbe identified by verifying that the sphere equivalent refraction (SEQ)of the eye that is outside a predetermined range. An outlier measurementcan also be identified by verifying that the rate of change of SEQ ofthe eye based on temporally proximate measurements is greater than apredetermined rate. An outlier measurement can also be identified byverifying that the SEQ of the eye for a measurement while viewing a fartarget differs from a manifest refraction of the eye by more than apredetermined value. An outlier measurement can also be identified byverifying that the SEQ of the eye for a measurement while viewing a nearviewing target that differs from a manifest refraction of the eye minusa stimulus corresponding to the near viewing target by more that apredetermined value. An outlier measurement can also be identified byidentifying a measurement having a first wavefront fit error (WFFE) forthe eye that exceeds a second WFFE of the eye by more than apredetermined amount.

In many embodiments, the eye is subjected to different viewingconditions during the sequence of aberration measurements. The viewingconditions can include, for example, different illumination levels(e.g., a daytime illumination level, a nighttime illumination level). Inmany embodiments, a change of viewing condition induces an accommodationof the eye. In many embodiments, statistically-significant componentaberrations of the eye are determined and quantified for one or moreviewing conditions.

In many embodiments, the performance of a candidate correction for theeye is determined over different viewing conditions. For example, themethod can further include determining a performance of a candidateoptical correction for the eye over a plurality of the viewingconditions by using a merit function that assesses the candidate opticalcorrection relative to the plurality of the viewing conditions. In manyembodiments, the merit function includes at least one factor to accountfor a relative importance of at least one viewing condition. In manyembodiments, the performance of the candidate correction is determinedby assessing the candidate optical correction relative to the pluralityof viewing conditions over a portion of the eye corresponding to a pupilsize of the eye and a pupil location of the eye for the viewingcondition.

In many embodiments, a prescriptive optical correction for the eye isdetermined in response to the performances of a number of candidateoptical corrections for the eye. For example, the method can includedetermining a performance of each of a number of candidate opticalcorrections for the eye over each of a number of the viewing conditions,and determining a prescriptive optical correction for the eye inresponse to the determined performances for the candidate opticalcorrections.

In another aspect, a method is provided for configuring a contact lensfor an eye. The method includes obtaining a corrective prescription forthe eye, measuring a sequence of positions of a contact disposed on theeye relative to the eye, determining a statistical dispersion of thesequence of positions, and determining an optical correction toincorporate into the contact lens based on the corrective prescriptionand the statistical dispersion.

In many embodiments, a performance of a contact lens having a candidatecorrection is determined over a number of relative positions between thecontact lens and the eye. In many embodiments, the relative positionsused are based on the statistical dispersion. In many embodiments, aperformance of the contact lens is also determined for a number ofviewing conditions for at least one of the relative positions.

In many embodiments, the contact lens is configured by determining whichhigh-order corrections to exclude from the optical correction to beincorporated into the contact lens. For example, in many embodiments,the corrective prescription for the eye includes low-order andhigh-order corrections; and the step of determining an opticalcorrection to incorporate includes excluding at least one high-ordercorrection based on the statistical dispersion.

In another aspect, an optical diagnostic system is provided for an eyehaving a pupil. The system includes a sensing device for sensingaberrations of the eye for each of a sequence of aberrationsmeasurements of the eye, and a computer coupled with the sensing device.The computer includes a processor and a computer readable mediumcomprising instructions executable by the processor to identify anoutlier aberration measurement of the sequence of aberrationmeasurements of the eye and exclude the outlier aberration measurementfrom the sequence of aberration measurements to produce a qualifiedsequence of aberration measurements. In many embodiments, the sensingdevice comprises a wavefront sensor. In many embodiments, the wavefrontsystem determines a plurality of refractive coefficients correspondingto sensed aberrations of the eye for each measurement of the sequence ofmeasurements. In many embodiments, the computer readable medium furtherincludes instructions executable by the processor for determining aplurality of refractive coefficients corresponding to sensed aberrationsof the eye for each measurement of the sequence of measurements. In manyembodiments, the instructions are executable by the processor toformulate an optical correction for the eye in response to the qualifiedsequence of aberration measurements.

In many embodiments, the system registers the sequence of aberrationmeasurements with a location of the eye. For example, the computerreadable medium can store a relationship between a size of the pupil andthe location of the pupil, and can further include instructionsexecutable by the processor for determining a plurality of sizes of thepupil corresponding to the sequence of aberration measurements, andregistering the sequence of aberration measurements with a location ofthe eye by using the plurality of pupil sizes and the relationship.

In many embodiments, the system registers the sequence of aberrationmeasurements with an orientation of the eye. For example, the computercan further include an input receiving data from which eye orientationscorresponding to the sequence of aberration measurements can begenerated. And the computer readable medium can further includeinstructions executable by the processor for determining orientations ofthe eye in response to the eye orientation data, and registering theaberration measurements with an orientation of the eye by using thedetermined orientations. In many embodiments, the system furtherincludes a measurement device coupled with the input and measuring aposition of at least one of a natural feature of the eye or anartificial reference mark added to the eye so as to generate the eyeorientation data.

The system can identifying an outlier aberration measurement in variousways. For example, a sequence of coefficients corresponding to acomponent aberration of the eye can be processed to identify a outlieraberration measurement by, for example, detecting one or morecoefficients of the sequence that deviate significantly from theprevailing trend of the sequence of coefficients. Post-blink aberrationmeasurements that follow a blink of the eye by less than a predeterminedamount of time can be identified as outlier measurements and can then beexcluded or considered for exclusion. Identifying a blink can include atleast one of detecting a radius of the pupil that is less than apredetermined value, detecting a rate of change of the pupil that isgreater that a predetermined rate, or detecting a radius of the pupilthat is inconsistent with a linear interpolation based on nearbyqualified radius measurements of the pupil. An outlier measurement canbe identified by identifying a sphere equivalent refraction (SEQ) of theeye that is outside a predetermined range. An outlier measurement can beidentified by identifying a rate of change of SEQ of the eye that isgreater than a predetermined rate. An outlier measurement can beidentified by identifying a SEQ of the eye for a measurementcorresponding to viewing a far viewing target that differs from amanifest refraction of the eye by more than a predetermined value. Anoutlier measurement can be identified by identifying a SEQ of the eyefor a measurement corresponding to viewing a near viewing target thatdiffers from a manifest refraction of the eye minus a stimuluscorresponding to the near viewing target by more that a predeterminedvalue. An outlier measurement can be identified by identifying ameasurement having a first wavefront fit error (WFFE) for the eye thatexceeds a second WFFE of the eye by more than a predetermined amount.

In many embodiments, the system includes an input receiving data fromwhich a plurality of viewing conditions imposed upon the eye during thesequence of aberrations measurements can be determined. And the computerreadable medium can further includes instructions executable by theprocessor for determining the plurality of viewing conditions andstoring the plurality of viewing conditions in the computer readablemedium. The viewing conditions can include different illuminationlevels, for example, a daytime illumination level and/or a nighttimeillumination level. In many embodiments, a change from one of theviewing conditions to another of the viewing conditions induces anaccommodation of the eye. In many embodiments, statistically-significantcomponent aberrations of the eye are determined and quantified for oneor more viewing conditions.

In many embodiments, the system determines a performance of a candidatecorrection for the eye over different viewing conditions. For example,the computer readable medium can further include instructions executableby the processor for determining a performance of a candidate opticalcorrection for the eye over a plurality of the viewing conditions byusing a merit function that assesses the candidate optical correctionrelative to the plurality of the viewing conditions. In manyembodiments, the merit function includes at least one factor to accountfor a relative importance of at least one viewing condition. In manyembodiments, the performance of the candidate correction is determinedby assessing the candidate optical correction relative to the pluralityof viewing conditions over a portion of the eye corresponding to a pupilsize of the eye and a pupil location of the eye for the viewingcondition.

In many embodiments, a prescriptive optical correction for the eye isdetermined in response to the performances of a number of candidateoptical corrections for the eye. For example, the computer readablemedium can further include instructions executable by the processor fordetermining a performance of each of a plurality of candidate opticalcorrections for the eye over each of a plurality of the viewingconditions, and determining a prescriptive optical correction for theeye in response to the determined performances for the candidate opticalcorrections.

For a fuller understanding of the nature and advantages of the presentinvention, reference should be made to the ensuing detailed descriptionand accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates a simplified system of one embodimentof the present invention.

FIG. 2 is a simplified block diagram of an exemplary computer system inaccordance with an embodiment.

FIG. 3 schematically illustrates a plurality of modules that may carryout embodiments of the present invention.

FIG. 4 is a flow chart showing steps for aligning, registering, orfusing data in accordance with an embodiment.

FIG. 5 is a flow chart showing a measurement sequence that may be usedto acquire eye measurements with first and second measuring instrumentsin accordance with an embodiment.

FIGS. 6 to 9 show images taken via the measurement sequence of FIG. 5.

FIG. 10 is a flow chart representing a process for registering multipledatasets that do not have a common characteristic in accordance with anembodiment.

FIG. 11 is a diagram representing an eye and showing that as the pupilcontracts, it also shifts in position.

FIG. 12 schematically illustrates a relationship between pupil size andlocation as derived from images of the eye under scotopic/mesopicconditions and photopic conditions, and also shows determination of awavefront sensor pupil position from a pupil size identified usingwavefront aberrometry data, combined with the relationship.

FIG. 13 is a flow chart schematically illustrating a method ofindirectly registering optical datasets of an eye, in accordance withmany embodiments.

FIG. 14 illustrates exemplary pupil positions for a range of pupilsizes, in accordance with many embodiments.

FIG. 15A illustrates a wavefront measurement system in accordance withmany embodiments.

FIG. 15B illustrates another wavefront measurement system in accordancewith many embodiments.

FIG. 16 illustrates Zernike polynomial shapes.

FIG. 17A illustrates a modal approximation of a wavefront surface.

FIG. 17B illustrates a zonal approximation of a wavefront surface.

FIG. 18 shows method steps for optically diagnosing an eye using asequence of aberration measurements, in accordance with manyembodiments.

FIG. 19A illustrates a sequence of accommodation measurements of a youngeye, in accordance with many embodiments.

FIG. 19B illustrates outlier accommodation measurements caused by blinksand partial blinks, in accordance with many embodiments.

FIG. 19C illustrates a qualified sequence of accommodation measurementsobtained by excluding outlier accommodation measurements, in accordancewith many embodiments.

FIG. 20A shows a difference between a zonal approximation of a wavefrontsurface and a modal approximation of a wavefront surface for a typicalwavefront measurement that is closely approximated by a modalapproximation, in accordance with many embodiments.

FIG. 20B is a slope residual map showing low residual fit error betweena modal approximation of the wavefront surface of the wavefrontmeasurement of FIG. 20A, in accordance with many embodiments.

FIG. 20C shows a difference between a zonal approximation of a wavefrontsurface and a 6^(th) order modal approximation of a wavefront surfacefor a wavefront measurement influenced by a tear film, in accordancewith many embodiments.

FIG. 21 illustrates an exemplary variation over time of a sequence ofcoefficients corresponding to a component aberration of a sequence ofaberration measurements, in accordance with many embodiments.

FIG. 22 shows method steps for configuring a contact lens, in accordancewith many embodiments.

DETAILED DESCRIPTION

In the following description, various embodiments of the presentinvention will be described. For purposes of explanation, specificconfigurations and details are set forth in order to provide a thoroughunderstanding of the embodiments. However, it will also be apparent toone skilled in the art that the present invention may be practicedwithout the specific details. Furthermore, well-known features may beomitted or simplified in order to not obscure the embodiment beingdescribed.

Embodiments herein provide devices, systems, and methods that facilitateoptical analysis, particularly for the diagnosis and treatment ofrefractive errors of the eye. Embodiments of the invention facilitatethe use of multi-modal diagnostic instruments and instrument systems,making it easier to acquire and fuse (e.g., synthesize) data fromdifferent measurements of the eye. For example, wavefront aberrometrymay be fused with corneal topography, optical coherence topography andwavefront, optical coherence topography and topography, pachymetry andwavefront, etc. While some of these different optical datasets may beobtained simultaneously, it is often difficult and/or disadvantageous toattempt to acquire the images or other data at exactly the same time.Embodiments herein permit registration of multiple datasets frommeasurements regardless of the sequence the measurements were taken.

Acquiring and fusing data from different measurements of the eye havesignificant potential advantages. For example, wavefront aberrometry andcorneal topography may be used separately to each provide a beneficialrefractive prescription, but the registration and combination ofinformation from both measurements may provide improved refractiveprescriptions and the like. These prescriptions may be used, forexample, with a laser surgery system.

Additional embodiments herein provide for the determination ofstatistically-significant aberration of an eye by analyzing a sequenceof aberration measurements of the eye. The statistically-significantaberrations can be determined for different viewing conditionsincluding, for example, different illumination levels and differentviewing distances. The statistically-significant aberrations can be usedto formulate one or more candidate optical corrections. And the one ormore candidate corrections can be evaluated with respect to theaberrations of the eye for one or more viewing conditions. A meritfunction can be used to rate the performance of a candidate correction.And the merit function can include one or more factors to account for arelative importance of at least one viewing condition.

The determination of statistically-significant aberrations hassignificant potential advantages. For example, by distinguishing betweenstatistically-significant and non-significant aberrations, the resultingcorrection may more accurately correct aberrations of the eye byavoiding the correction of transient aberrations arising from transientdynamics of the eye. Determining statistically-significant aberrationsfor different viewing conditions provides data that enables theselection of an optical correction that provides a more optimumcompromise with regard to the various viewing conditions faced by aperson (e.g., nighttime, daytime, distance vision, close vision, etc.).

Additional embodiments herein provide for the configuration of a contactlens to reflect observed levels of relative movement between the contactlens and an eye. A sequence of positions of a contact relative to theeye can be measured and analyzed to determine a statistical dispersionof the relative positions. The resulting statistical dispersion can beused to select which optical corrections to include in the contact lens.

Such a configuration approach for a contact lens has significantpotential advantages. For example, a common current practice forconfiguring a contact lens is to only include low-order corrections inthe contact lens (e.g., first and second order corrections). Bydetermining the dispersion of the relative movements, it may be possibleto include higher-order corrections into the contact lens. For example,where the observed motion is between 0.5 mm and 1.0 mm, it may bepossible to include third order corrections into the contact lens. Wherethe observed motion is less than 0.5 mm, it may be possible to includeeven higher-order corrections into the contact lens (e.g., fourth order,fifth order, and/or sixth order). Where higher-order corrections can beincluded, an improved vision correction may result.

FIG. 1 schematically illustrates a simplified system of one embodimentof the present invention. Advantageously, elements, components,subsystems, and method elements to be used in embodiments of the presentinvention can be taken and/or derived from a number of known structuresand methods. Exemplary constituent elements may include structuresand/or techniques found in or derived from those of U.S. Pat. No.7,044,602 in the name of Chernyak and entitled “Methods and Systems forTracking a Torsional Orientation and Position of an Eye”; US PatentApplication Publication No. 2004/0263785 in the name of Chernyak andentitled “Methods and Devices for Registering Optical MeasurementDatasets of an Optical System”; and/or US Patent Application PublicationNo. 2006/0215113 in the name of Chernyak and entitled “Pupilometer forPupil Center Drift and Pupil Size Measurements at Differing ViewingDistances”; the full disclosures of which are incorporated herein byreference. Alternative embodiments may use, for example, differentcommercially available pupil location and/or size measurementstructures, different iris or other natural or artificial rotationalmarkers, or the like, so that not all aspects of the present inventionwill necessarily be limited to these particular components.

In the embodiment shown in FIG. 1, the system includes a firstmeasurement instrument 10, a second measurement instrument 16, and alaser system 15. In an embodiment, the first measurement instrument 10is a wavefront measurement device 10 that measures aberrations and otheroptical characteristics of an ocular or other optical tissue system. Thedata from such a wavefront measurement device may be used to generate anoptical surface from an array of optical gradients. It should beunderstood that the optical surface need not precisely match an actualtissue surface, as the gradients will show the effects of aberrationswhich are actually located throughout the ocular tissue system.Nonetheless, corrections imposed on an optical tissue surface so as tocorrect the aberrations derived from the gradients should correct theoptical tissue system. As used herein terms such as “an optical tissuesurface” may encompass a theoretical tissue surface (derived, forexample, from wavefront sensor data), an actual tissue surface, and/or atissue surface formed for purposes of treatment (for example, byincising corneal tissues so as to allow a flap of the corneal epitheliumto be displaced and expose the underlying stroma during a LASIKprocedure).

The second measurement instrument 16 may include a corneal topographer.Corneal topographer 16 may be used to diagnose and examine the cornealsurface. Corneal topographer 16 typically includes an imaging device 18,such as a frame grabber that takes images of the cornea. The imagesobtained by the frame grabber are analyzed by a computer system 19, andthe computer system may generate one or more graphical and/or tabularoutputs, including three dimensional topographical maps. Cornealtopographer 16 may determine the contours of the corneal surface bymeasuring the elevations and depressions in the corneal surface. Oneexample of a corneal topographer 16 utilizes a laser, LED or other lightsource that maps a series of dots on the surface of the cornea.Reflected light rays of the dots are reflected to a sensor, which inturn provides data to the computer system 19 regarding the reflecteddots. The computer system 19 forms a corneal elevation map from thedata. An example of such a system, sometimes called a full gradienttopographer, is the iDESIGN ADVANCED WAVESCAN STUDIO System, which is atleast partially described in co-pending U.S. patent application Ser. No.12/347,909, filed Dec. 31, 2008, and entitled “Systems and Methods forMeasuring the Shape and Location of an Object,” and which is hereinincorporated by reference.

Another example of a corneal topographer is the HUMPHREY ATLAS CornealTopographer, from Zeiss Humphrey Systems, of Dublin, Calif., which is aninstrument that uses Placido disk technology to generate images of thecorneal surface. The ring-based corneal topographer 16 may be based on amethod that captures the reflection of rings of light off of the surfaceof the cornea and measures the distortion in the reflected light. Adetector (not shown) captures the reflected images and computer system19 processes the data, and displays the information in one or moreformats selected by the user. For example, corneal topographer 16 mayprovide an axial map (which describe the radius of the curvature of thecornea relative to optic axis), curvature maps (which portray the radiusof the curvature independent of the optic axis), and/or elevation maps(which illustrate the radius relative to a reference sphere).

As can be appreciated, the full gradient topographer and the HUMPHREYATLAS topographer are merely two examples of corneal topographers thatmay be used with the present invention. Other corneal topographers soldby Topcon Medical Systems, Dicon Diagnostics, Haag-Streit, EyeQuip,Tomey Corp., Bausch & Lomb, Carl Zeiss Ophthalmic Systems, Nidek, andLaser Sight may be used with the present invention. Some systems andmethods for measuring a corneal topography of an eye are described inU.S. Pat. Nos. 4,761,071, 4,995,716, 5,406,342, 6,396,069, 6,116,738,4,540,254 and 5,491,524, the full disclosures of which are incorporatedherein by reference.

In an embodiment, the corneal topographer 16 includes an irisregistration component, which may include cameras and pupilometermeasurement features, such as described in US Patent ApplicationPublication No. 2006/0215113 in the name of Chernyak and entitled“Pupilometer for Pupil Center Drift and Pupil Size Measurements atDiffering Viewing Distances,” the full disclosure of which isincorporated herein by reference. The iris registration features mayalternatively be included with the first measurement instrument 10, oras a completely separate system. In addition, although shown as twoseparate measurement instruments 10 and 16, the features of the firstand second measurement instruments may be provided on a single system.

Furthermore, while embodiments herein focus on registering datasets ofan eye from a wavefront measurement instrument, such as the firstmeasurement instrument 10, and a corneal topographer, such as the secondmeasurement instrument 16, embodiments of the present invention areequally applicable to registering datasets obtained by a variety ofother optical measurement instruments. For example, the presentinvention may be used to fuse data from optical coherence topography andwavefront, optical coherence topography and topography, pachymetry andwavefront, and the like.

The laser surgery system 15 surgery system 15 includes a laser assembly12 that produces a laser beam 14. Laser assembly 12 is optically coupledto laser delivery optics (not shown), which directs laser beam 14 to aneye E of a patient. An imaging assembly 20, such as a microscope ismounted on the delivery optics support structure to image a cornea ofeye E during the laser procedure.

Laser assembly 12 generally comprises an excimer laser source, typicallycomprising an argon-fluorine laser producing pulses of laser lighthaving a wavelength of approximately 193 nm. Laser assembly 12 willpreferably be designed to provide a feedback stabilized fluence at thepatient's eye, delivered via delivery optics. Although an excimer laseris the illustrative source of an ablating beam, other lasers may beused.

Laser assembly 12 and delivery optics will generally direct laser beam14 to the eye E under the direction of a computer system 22. Computersystem 22 will generally selectively adjust laser beam 14 to exposeportions of the cornea to the pulses of laser energy so as to effect apredetermined sculpting of the cornea and alter the refractivecharacteristics of the eye. In many embodiments, both laser beam 14 andthe laser delivery optical system will be under computer control ofcomputer system 22 to affect the desired laser sculpting process so asto deliver the customized ablation profile, with the computer systemideally altering the ablation procedure in response to inputs from theoptical feedback system. The feedback will preferably be input intocomputer system 22 from an automated image analysis system, or may bemanually input into the processor by a system operator using an inputdevice in response to a visual inspection of analysis images provided bythe optical feedback system. Computer system 22 will often continueand/or terminate a sculpting treatment in response to the feedback, andmay optionally also modify the planned sculpting based at least in parton the feedback.

While embodiments herein are described primarily in the context ofimproving diagnosis and treatment of the refractive errors of the eyeusing a laser eye surgery system 15, it should be understood the presentinvention may be adapted for use in alternative diagnosis of otheroptical systems, eye treatment procedures, and optical systems such asfemtosecond lasers and laser treatment, infrared lasers and lasertreatments, radial keratotomy (RK), scleral bands, follow up diagnosticprocedures, and the like.

FIG. 2 is a simplified block diagram of an exemplary computer system 17,19, 22 in accordance with an embodiment. The computer system typicallyincludes at least one processor 60 which communicates with a number ofperipheral devices via a bus subsystem 62. These peripheral devices mayinclude a storage subsystem 64, comprising a memory subsystem 66 and afile storage subsystem 68, user interface input devices 70, userinterface output devices 72, and a network interface subsystem 74.Network interface subsystem 74 provides an interface to a communicationnetwork 75 for communication with other imaging devices, databases, orthe like.

The processor 60 performs the operation of the computer systems 17, 19,22 using execution instructions stored in the memory subsystem 66 inconjunction with any data input from an operator. Such data can, forexample, be input through user interface input devices 70, such as thegraphical user interface. Thus, processor 60 can include an executionarea into which execution instructions are loaded from memory. Theseexecution instructions will then cause processor 60 to send commands tothe computer system 17, 19, 22, which in turn control the operation ofthe first measurement instrument 10, the second measurement instrument16, and the laser system 15. Although described as a “processor” in thisdisclosure and throughout the claims, the functions of the processor maybe performed by multiple processors in one computer or distributed overseveral computers.

User interface input devices 70 may include a keyboard, pointing devicessuch as a mouse, trackball, touch pad, or graphics tablet, a scanner,foot pedals, a joystick, a touch screen incorporated into the display,audio input devices such as voice recognition systems, microphones, andother types of input devices. In general, use of the term “input device”is intended to include a variety of conventional and proprietary devicesand ways to input information into the computer system. Such inputdevices will often be used to download a computer executable code from acomputer network or a tangible storage media embodying steps orprogramming instructions for any of the methods of the presentinvention.

User interface output devices 72 may include a display subsystem, aprinter, a fax machine, or non-visual displays such as audio outputdevices. The display subsystem may be a cathode ray tube (CRT), aflat-panel device such as a liquid crystal display (LCD), a projectiondevice, or the like. The display subsystem may also provide non-visualdisplay such as via audio output devices. In general, use of the term“output device” is intended to include a variety of conventional andproprietary devices and ways to output information from the computersystem to a user.

Storage subsystem 64 stores the basic programming and data constructsthat provide the functionality of the various embodiments. For example,database and modules implementing the functionality of embodimentsdescribed herein may be stored in storage subsystem 64. These softwaremodules are generally executed by processor 60. In a distributedenvironment, the software modules may be stored in a memory of aplurality of computer systems and executed by processors of theplurality of computer systems. Storage subsystem 64 typically comprisesmemory subsystem 66 and file storage subsystem 68.

Memory subsystem 66 typically includes a number of memories including amain random access memory (RAM) 76 for storage of instructions and dataduring program execution and a read only memory (ROM) 78 in which fixedinstructions are stored. File storage subsystem 68 provides persistent(non-volatile) storage for program and data files, and may include ahard disk drive, a floppy disk drive along with associated removablemedia, a Compact Digital Read Only Memory (CD-ROM) drive, an opticaldrive, DVD, CD-R, CD-RW, or removable media cartridges or disks. One ormore of the drives may be located at remote locations on other connectedcomputers at other sites coupled to the computer system. The databasesand modules implementing the functionality of the present invention mayalso be stored by file storage subsystem 68.

Bus subsystem 62 provides a mechanism for letting the various componentsand subsystems of the computer system communicate with each other asintended. The various subsystems and components of the computer systemneed not be at the same physical location but may be distributed atvarious locations within a distributed network. Although bus subsystem62 is shown schematically as a single bus, alternate embodiments of thebus subsystem may utilize multiple busses.

The computer system itself can be of varying types including a personalcomputer, a portable computer, a workstation, a computer terminal, anetwork computer, a module in the imaging unit, a mainframe, or anyother data processing system. Due to the ever-changing nature ofcomputers and networks, the description of the computer system depictedin FIG. 2 is intended only as a specific example for purposes ofillustrating one embodiment of the present invention. Many otherconfigurations of the computer system are possible having more or lesscomponents than the computer system depicted in FIG. 2.

FIG. 3 schematically illustrates a plurality of modules 80 that maycarry out embodiments of the present invention. The modules 80 may besoftware modules, hardware modules, or a combination thereof. If themodules are software modules, the modules will be embodied on a computerreadable medium and processed by a processor 60 in any of computersystems of the present invention.

A first dataset from a first instrument will be received by module 82.The first dataset is typically an optical measurement and/or image of anoptical system, such as an eye. For example, in one embodiment, theoptical measurement is in the form of a wavefront measurement of apatient's eye. Such a wavefront measurement may be obtained by thewavefront measurement assembly 11.

A second dataset from a second instrument is received by module 84. Thesecond dataset is also typically an optical measurement and/or image ofthe same optical system. For example, in one embodiment, the secondoptical measurement is in the form of a corneal topographical map of thepatient's eye E, from the imaging device 18.

A third and fourth modules 86, 88 receive third and fourth datasets,respectively, which, in an embodiment, are also optical measurementsand/or images of an optical system, such as an eye E. As describedbelow, these additional datasets provide information that may be used tofuse the first and second datasets, and/or may provide additional datathat may be fused with the first and second datasets. Although theembodiment shown includes the two modules 86, 88, a single module may beused, and a single dataset, depending upon the information utilized tofuse the first and second datasets and/or to be fused with the first andsecond datasets. In an embodiment, the third dataset is an irisregistration scotopic/mesopic image from the iris registration component24. This image measures the pupil size, position and shape, and theouter iris boundary position and size in low light conditions. In anembodiment, the fourth dataset is an iris registration photopic imagefrom the iris registration component 24. This image is used to measurethe pupil size, position and shape, and the outer iris boundary positionand size in bright light conditions. These images may be obtained by theiris registration component 24, for example.

The first, second, third and fourth datasets may be transmitted from thefirst instrument 10 and second instrument 16 over a communicationnetwork, or the datasets from each of the devices may be stored on acomputer readable medium and uploaded to the computer system thatprocesses the modules 80.

In order to take maximum advantage of the first, second, third and/orfourth datasets for diagnosis of refractive errors of the eye and forcorneal treatment planning, the datasets may be registered, or the datafrom the images fused. Consequently, the first, second, third and fourthdatasets may be transmitted to a registration module 90 where one ormore image processing algorithms are applied to the datasets to registerthe datasets.

Some measurement instruments may not produce datasets that are readilyregistered. Incompatibility may be based upon the fact that the twodatasets are taken at different times, and/or movement of the eye mayoccur between measurements. To address such problems, a singlemeasurement instrument might acquire multiple different types ofophthalmic measurements simultaneously, using synchronized cameras orthe like. Although simultaneous recording might facilitate registration,it is often difficult, impossible, or undesirable to acquire the imagesat exactly the same time. For example, different illumination states maybe desired for different types of measurements, requiring measurementsbe taken at different times. For example, in some ring-based measurementsystems, corneal topography (CT) illumination may be incompatible withiris registration imaging via wavefront, because wavefront may benefitfrom a largest pupil size (thus scotopic), but the corneal topographyillumination shrinks the size of the pupil.

In accordance with an embodiment, a relationship module 92 is providedthat allows datasets of the eye to be registered, whether taken by asingle measurement instrument having a single eye measurement location,or by separate measurement devices or the like having separate eyemeasurement locations. Moreover, in accordance with an embodiment, themultiple measurements may be taken at different moments in time, and themeasurements may be registered together despite movement of the eyebetween the eye measurements. Thus, embodiments described herein maysignificantly facilitate use of the combination of some eye measurementsystems not typically combinable for simultaneous measurement, and thusenhance measurement accuracy.

As described in more detail below, the relationship module 92 determinesproper registration and alignment between multiple data types so thatthese data may be used together (fused) to produce a combinedmeasurement. In embodiments, the relationship module 92 removeslimitations of measurement sequence and illumination in the registrationprocess. In accordance with one embodiment, as further described below,the relationship module 92 identifies, and corrects for, changes in thepupil size, position and shape during the measurement process, andthereby maintains accurate alignment between the various measurements.

FIG. 4 is a flow chart showing steps for registering or fusing data inaccordance with an embodiment. Beginning at step 100, the first andsecond measuring instruments 10 and 16 are used to acquire measurementsof the eye. The measurements include image datasets. A sequence foracquiring measurements is described together with FIG. 5.

FIG. 5 is a flow chart showing a measurement sequence that may be usedto acquire eye measurements with the first and second measuringinstruments 10, 16 in accordance with an embodiment. Beginning at step200, the second measuring instrument 16 is aligned using the cornealtopography image. At step 202, the corneal topography image is acquired.

At step 204, the first measuring instrument 10 is used to auto refract,for example using the wavefront measurement assembly 11. At step 206, awavefront image is acquired.

At step 208, illumination is set to take a scotopic image. At step 210,the scotopic image is acquired. At step 212, illumination is set to takea photopic image, and at step 214, after a delay to allow the pupil tocontract, the photopic image is acquired.

After the sequence in FIG. 5, the system has four different images.Acquisition of these images does not have to be in the sequence providedin FIG. 5. In addition, the images need not be taken at the same time,and they may have different illumination from image to image. A timedifference between measurements may result in the eye moving to adifferent location and a change in illumination may result in the pupilchanging in size and relative position.

FIGS. 6 to 9 show images taken via the measurement sequence of FIG. 5.FIG. 6 is the iris registration scotopic/mesopic image, which measuresthe pupil size, position and shape, and the outer iris boundary positionand size in low light conditions. The image contains feature detail ofthe iris. FIG. 7 is the wavefront aberrometer image, which measureslight scattered or reflected from a point on the retina. FIG. 8 is theiris registration photopic image, which measures the pupil size,position and shape, and the outer iris boundary position and size inbright light conditions. The image contains feature detail of the iris.FIG. 9 is the corneal topography image.

Returning now to FIG. 4, after the measurements are obtained in step100, at step 102, possible data fusion relationships are evaluated.These data fusion relationships are data types that are available tomultiple images, so that registration between the multiple images may bemade by using the commonly available data types. Preferably, acharacteristic common to all images is used for data fusion.

In some embodiments, the data may be fused by adjusting data locationand orientation. Alternative embodiments may be fused by adjusting datalocation and limiting eye rotation about the optical axis, often byavoiding gross movement of the patient between measurements (such as byusing a common eye measurement location) and by limiting the timebetween data acquisition for the different measurements. Fortunately,the time sequence for taking multiple measurements on an exemplarymulti-modal system may be short, with total image acquisition time forobtaining a plurality of different types of measurements optionallytaking less than 30 seconds, often less than 10 seconds, preferably lessthan 5 seconds, and in some cases taking about 4 seconds or less than asecond. Even images/measurements taken with illumination sufficientlydifferent to alter a size of the pupil may be taken at times that arequite close, the differences between the image acquisition times forwavefront and corneal topography, for example, typically being within 1second, and in exemplary embodiments being within ⅕ of a second, 1/10 ofa second, or 1/30 of a second. Under such conditions, rotation of theeye between measurements may be negligible.

In embodiments, rotational adjustments between datasets may beidentified using simultaneous pupil shape information (such as may beavailable from the wavefront data), simultaneous retinal data(optionally including images of vessels or other landmarks obtainedduring wavefront data acquisition), simultaneous iris data obtained froman co-axial or an off-axis camera, or the like.

Thus, a number of different systems exist for registration of images toeach other when the images have a common characteristic. However, due tothe difference measurement principles used to create images, acharacteristic common to all images may not be available. It may besufficient, however, to register images together in subsets, and thenregister subsets to other subsets until all images are registered toeach other. For example, FIG. 10 is a flow chart representing a processfor registering multiple datasets that do not have a commoncharacteristic in accordance with an embodiment. At step 300, the imagesare acquired. At step 302, two images are registered with each otherusing one or more first features, thus creating a first registered imagepair. At step 304, two images, at least one being different from thefirst set, are registered with each other using one or more secondfeatures, thus creating a second registered image pair. At step 306, thetwo registered image pairs are registered with each other using oneimage from each pair and one or more third features different from thefirst features to register the images. After the process in FIG. 10, allimages have a determined spatial relationship with each other.

The process of FIG. 10 works particularly well when two datasets aredifficult to register with each other because the two datasets do notinclude common characteristics. In such a situation, an image or a groupof images may act as intermediary datasets for the two datasets that aredifficult to register together. For example, for the system shown inFIG. 1, as further described below, the corneal topography image isdifficult to register directly to the wavefront image because the twoimages do not contain any common features. The pupil is visible in thewavefront image as the region illuminated, but it is potentiallyobscured in the corneal topography image by the array of reflected spotsor the reflected Placido rings. Furthermore, the wavefront and cornealtopography images are taken under different lighting conditions and maybe taken at widely different times (hence the eye may be in a differentposition). Thus, using the process in FIG. 10, the corneal topographyimage and the wavefront image may each be separately registered to anintermediary dataset, and through those two separate registrations, areultimately registered to each other. In other words, the cornealtopography image is registered to the intermediary dataset, which inturn is registered to the wavefront image. In such a system, the twoimages that are registered at step 302 include the corneal topographyimage and the intermediary dataset, and the two images that areregistered at step 304 are the wavefront image and the intermediarydataset.

Thus, returning to FIG. 4, a relationship is established at step 104,such as the use of the intermediary dataset described above. At step106, the first dataset is fused using the relationship, and at step 108,the second dataset is fused using the relationship. After the steps inFIG. 4, all images are fused.

Data that is available from the images differs based upon the imagetype. With image recognition techniques it is possible to find theposition and extent of various features in an image. Turning now to thespecific four images captured in FIG. 5, for the iris registrationimages, features that are available include the position, size and shapeof the pupil, the position, size and shape of the outer iris boundary(OIB), salient iris features (landmarks) and other features as aredetermined to be needed.

In the iris registration images, it is possible, without interferencefrom any of the various reflections (iris illumination sources) to findthe pupil position, size and shape accurately. This is facilitated byarrangement of the system components such that the illumination sourcesare near the optical axis, and thus the reflections are near the centerof the pupil, and thus do not interfere with finding the pupil's edge.Information from different landmarks may be correlated, for example, byaccurately locating the outer iris boundary and/or iris landmarksrelative to the pupil. This may help allow a pupil location to bedetermined from another image in which the pupil itself is not visible,optionally with greater accuracy than may be provided by relying on animage of the limbus alone (as the limbus may appear as a gradualboundary, rather than having a sharp boundary).

In the corneal topography image, however, it may be advantageous tomeasure the topography as close to the center as possible. In generalthe corneal topography projected pattern covers the full pupil,including the center and the edge of the pupil. This pattern mayinterfere with finding the pupil position, size and shape accurately.Furthermore, the illumination is generally adjusted to optimize thecorneal topography image for detecting the reflected pattern. Thisillumination is not necessarily the same, nor optimized for, thedetection of the pupil information. Therefore, it may be desirable tofind a different feature in the corneal topography image to use forregistration information.

It is noted that the strong curvature of the cornea is such that only alimited coverage of the corneal area is often measurable by cornealtopography. Usually this coverage includes the pupil and central area,but often does not extend to the outer iris boundary. Thus no projectedpattern may be evident in the images near the outer iris boundary. Thevisible peripheral portion of the iris image included in the cornealtopography image may be used for registration, for example, to helpaccurately locate the pupil (even if the pupil image is not readilyseen), to help identify the torsional orientation of the eye about theoptical axis of the eye, and/or the like.

Thus it is possible to register the outer iris boundary information thatis found in the corneal topography image with that from the irisregistration image. The relative position of these two outer irisboundary measurements can be used to determine the correct relativeposition of the measurement information. Furthermore, the outer irisboundary is a fixed feature in the eye, and does not change with time,or with measurement type.

However, the wavefront aberrometry image generally has no features thatcorrespond to the outer iris boundary. Thus some other feature willoften be used to register this image to other images. In wavefrontaberrometer, the pupil is back illuminated by the scattering source onthe retina, with the retina aperturing the aberrometry data. Thus, thesize, shape, and location of the pupil can be accurately determined. Theposition of the wavefront pupil can thus be registered to the positionof the measured pupil from the iris image.

Thus the wavefront data and the corneal topography data can beseparately registered to features on the iris registration image. Theiris registration image can be treated as a reference image, and boththe wavefront data and the corneal topography data can be registered tocoordinates that are centered on this image.

The process of FIG. 10 may be used, therefore, to register the wavefrontdata to the corneal topography data, using the iris registration imageas the intermediary. There remains at least one further difficulty,however. That is that the pupil might change position as a function ofsize. Since the illumination is in general different between acquisitionof the wavefront and the iris images, it may be that the pupil haschanged substantially in size between the two acquisitions.

This issue may be addressed by interpolating the size of the pupil inthe wavefront data onto information known about the pupil size from theiris registration information so as to arrive at the position of thepupil for the wavefront. Note that there are two iris images that can beacquired. These differ in the illumination that is provided. Thescotopic (or mesopic) image is taken with minimum illumination,preferably in the IR or Near IR wavelengths of light so that the eyedoes not respond to illumination by changing in size or position. It isusually desirable to maximize the pupil size during the wavefront andscotopic image acquisition.

The other image is the photopic image. It is acquired by first turningon a bright visible (e.g., green) source of illumination, waiting forthe eye to respond, and then acquiring an iris image. This results in animage where the pupil is smaller than that of the scotopic image.

As the pupil contracts, it also shifts in position. This relationship isshown in FIG. 11. Pupil P contracts and/or expands with changes inbrightness or illumination, with these changes in illuminationoptionally including changes in the brightness of the object or targetbeing viewed, changes in the ambient light around the viewing target,and the like.

Along with changes in the overall size of pupil P when the eye E issubjected to different viewing conditions, the location of the pupilcenter C may also change. It should be noted that this change inlocation of the pupil center may be separate from and in addition to anyoverall movement of the eye. In other words, even if the eye E were toremain at an overall fixed location in space so that the cornea and theretina of the eye did not move, as the pupil P contracts from a firstpupil configuration P to a smaller pupil configuration P, the center Cof the pupil may undergo a corresponding change in location to a newpupil center C′. This change in pupil center location is encompassedwithin the term “pupil center drift” as that term is used herein.

The position and size of the pupil are correlated. That is, as the pupilcontracts, it shifts. So with two measurements of the pupil, it ispossible to determine this correlation and describe it as a linear shift(which it will be to a good approximation). So for any known ormeasurement pupil size, from these two images it will be possible todetermine a corresponding pupil position. In an embodiment, one of thetwo images is obtained from a corneal topographer. Alternativeembodiments may determine the relationship of pupil size and positionusing additional images (such as to determine a curved relationship), bycontinuously or dynamically measuring location and pupil size duringchanges in illumination, or the like. In addition, in an embodiment, apupil image is obtained from the corneal topographer, and that image isused to determine the relationship between the pupil size and location.

Thus, with both a photopic image and a scotopic/mesopic image, arelationship may be established between pupil size and position. Thus,using the pupil size obtained in the wavefront image, it is possible todetermine the pupil position when the wavefront image was acquired. Tothis end, the pupil position is described as a linear function of thepupil size by evaluating the pupil size and position from thescotopic/mesopic and photopic images as shown in FIG. 12. Then thecorresponding pupil size calculated from the wavefront sensor image isused to “look up” the position of the pupil on this curve. Thiscorrelation correctly allows for the appropriate pupil position shift asthe eye changes it shape. The offset from the center (or other referencepoint) of the wavefront image relative to the iris registration imagecan be used to provide the exact relationship between the variousimages, taking all the phenomena into account. FIG. 14 shows exemplarypupil positions for a range of pupil sizes, and illustrates an exemplarylevel of variability over the range of pupil sizes.

Thus, using the above, the relationship established pursuant to step 404includes: registering the outer iris boundary information that is foundin the corneal topography image with that from the iris registrationimage, and registering the position of the wavefront pupil to the properposition as interpolated from the iris images. These functions areperformed, for example, via the registering module 90 and therelationship module 92.

During embodiments of the multi-modal eye diagnosis described herein andshown schematically in FIG. 13, data fusion is optionally achieved whenthe correct spatial relationship can be established between some orpreferably all of the following four datasets:

1. corneal topography image, associated corneal elevation map or dataderived from the image or elevation map (such as local gradients of thecorneal surface)

2. wavefront image, associated reconstructed ocular wavefront or dataderived from the image or wavefront reconstruction (such as thewavefront decomposition into function sets (e.g., Fourier and zonalreconstruction, and Zernike and Taylor polynomial reconstruction)

3. Scotopic eye image or data derived from the scotopic eye image (suchas scotopic pupil shape, scotopic pupil size, scotopic pupil centroidposition, limbus or outer iris boundary, iris pattern, blood vesselpattern, or artificial landmarks such as flap cut, intrastromal bubble)

4. Photopic eye image or data derived from the photopic eye image (suchas photopic pupil shape, photopic pupil size, photopic pupil centroidposition, limbus or outer iris boundary, iris pattern, blood vesselpattern, or artificial landmarks such as flap cut, intrastromal bubble)

For embodiments invention disclosed herein, as shown in FIG. 13,registering of the multiple datasets may be used in the followingmanner. First, the relationship between pupil position and diameter isestablished from the scotopic and photopic images, as shown in FIG. 12.The pupil size is measured on the wavefront image (along with therelative wavefront offset) by back illuminating the pupil by thescattering source on the retina, with the retina aperturing theaberrometry data (Detections 02 and 03, FIG. 13). Thus, the size, shape,and location of the pupil can be accurately determined. For the pupilsize determined from the wavefront measurement, the relative position onthe iris images is determined using the previously establishedrelationship of size to position (FIG. 12). Note that the wavefrontpupil size is not necessarily between the pupil sizes of the photopicand scotopic images, and may be smaller than the pupil in the photopicimage, larger than the pupil in the scotopic image, or the same size asthe pupil in either of these images. As long a relationship between sizeand position is established, the position of the wavefront can bedetermined or estimated. After the position is determined or estimated,ambiguity as to the position of the images is removed, or at leastreduced, and all are thus registered correctly (Registration R2, FIG.13).

The registration step R1 is now described. First, the iris landmarks aredetected from the CT image 11. To do this step, the outer circularboundary C1 of the corneal topography spot pattern is detected. A secondcircular boundary C2 is chosen to include the limbus border. C1 and C2are concentric and form a ring of iris structure. A coordinatetransformation from cylindrical to Cartesian coordinates isperformed—the iris structure ring is unwrapped into an iris structurestrip. The iris structure strip is filtered with a Sobel y-gradientfilter for edge detection followed by binarization of the image.Additional aspects of determining the center of the limbus and/or pupilmay be understood with reference to U.S. Pat. No. 7,044,602 in the nameof Chemyak, the full disclosure of which is incorporated herein byreference.

The same steps are performed for the photopic eye image 14. Thetranslational offset between the two limbus centers is now known. Arotational offset between the two images 11, 14 can be computed bycorrelation of the two iris feature strips with iterations around scaledue to elastic deformation of the iris features forconstricting/dilating pupils. Thus, the photopic eye image 14 and the CTimage 11 can be registered to each other.

The photopic and scotopic eye measurements are registered to each otherusing known methods, for example via use of iris landmarks (Registration3). Afterwards, all images and data from the images may be fused.

Wavefront Measurement Systems

In many embodiments, an aberrometer system, for example, a wavefrontmeasurement system, is used to assess the optical aberrations that existin an eye. Wavefront measurement systems work by measuring the way awavefront of light passes through the various refractive or focusingcomponents of the eye, such as the cornea and crystalline lens. In oneapproach, a narrow beam of light is directed upon the retina of an eyeand its reflection emerges from the eye. In the case of an ideal eye,the emerging reflection is comprised of uniformly parallel beams oflight. However, in the case of a non-ideal eye, the emerging reflectionis comprised of non-parallel beams of light due to various opticalaberrations throughout the eye. Some wavefront measurements systems usean array of lenses and associated sensors to provide a collection ofmeasurements or gradients, each gradient indicating how much aparticular region of the emerging reflection deviates from the idealparallel path. The measured gradients can then be used to determine awavefront elevation map having the same gradients as the measuredgradients. The wavefront elevation map is a graphical representation ofthe optical aberrations in the eye, and, with regard to cornealalteration via ablation of the anterior surface of the cornea, isclosely correlated with the ablation profile that must be removed tocorrect the optical aberrations.

Referring now to FIG. 15A, one embodiment of a wavefront measurementsystem 430 is schematically illustrated in simplified form. In verygeneral terms, the wavefront measurement system 430 is configured tosense local slopes of light exiting the patient's eye. Devices based onthe Hartmann-Shack principle generally include a lenslet array to samplelight uniformly over an aperture, which is typically the exit pupil ofthe eye. Thereafter, the local slopes of the exiting light are analyzedso as to reconstruct the wavefront surface or map.

More specifically, the wavefront measurement system 430 includes animage source 432, such as a laser, which projects a source image throughoptical tissues 434 of an eye (E) so as to form an image 444 upon asurface of a retina (R). The image from the retina (R) is transmitted bythe optical system of the eye (e.g., the optical tissues 434) and imagedonto a wavefront sensor 436 by system optics 437. The wavefront sensor436 communicates signals to a computer system 422′ for measurement ofthe optical errors in the optical tissues 434 and, in many embodiments,determination of a defect-correcting prescription. The computer 422′ mayinclude the same or similar hardware as the computer system 17, 19, 22illustrated in FIGS. 1 and 2. The computer system 422′ may be incommunication with the computer system 22 that directs the laser surgerysystem 15, or some or all of the components of the computer system 22,422′ of the wavefront measurement system 430 and the laser surgerysystem 15 may be combined or separate. If desired, data from thewavefront sensor 436 may be transmitted to the laser computer system 22via the tangible media 429, via an I/O port, via a networking connectionsuch as an intranet or the Internet, or the like.

The wavefront sensor 436 generally comprises a lenslet array 438 and animage sensor 440. As the image from the retina (R) is transmittedthrough the optical tissues 434 and imaged onto the wavefront sensor436, the lenslet array 438 separates the transmitted image into an arrayof beamlets 442, and (in combination with other optical components ofthe system) images the separated beamlets 442 on the surface of thesensor 440. The sensor 440 typically comprises a charged coupled device(“CCD”) and senses characteristics of these individual beamlets, whichcan be used to determine the characteristics of an associated region ofthe optical tissues 434. In particular, where the image 444 comprises apoint or small spot of light, a location of a transmitted spot as imagedby a beamlet can directly indicate a local gradient of the lighttransmitted through the associated region of the optical tissue.

The eye (E) generally defines an anterior orientation (ANT) and aposterior orientation (POS). The image source 432 generally projects animage in a posterior direction through the optical tissues 434 onto theretina (R) as indicated in FIG. 15A. The optical tissues 434 transmitthe image 444 from the retina in the anterior direction toward thewavefront sensor 436. The image 444 transmitted through the opticaltissues 434 may be distorted by any imperfections in the eye's opticalsystem. Optionally, image source projection optics 446 may be configuredor adapted to decrease any distortion of image 444.

In some embodiments, the image source optics 446 may decrease low-orderoptical errors by compensating for spherical and/or cylindrical errorsof the optical tissues 434. High-order optical errors of the opticaltissues may also be compensated through the use of an adaptive opticelement, such as a deformable mirror (described below). Use of an imagesource 432 selected to define a point or small spot as the image 444upon the retina (R) may facilitate the analysis of the data provided bythe wavefront sensor 436. Distortion of the image 444 may be limited bytransmitting a source image through a central region 449 of the opticaltissues 434, which is smaller than a pupil 450, as the central portionof the optical tissues may be less prone to optical errors than aperipheral portion. Regardless of the particular image source structure,it will be generally be beneficial to have a well-defined and accuratelyformed image 444 on the retina (R).

In some embodiments, the measured wavefront data may be stored in acomputer readable medium 429 or a memory of the wavefront sensor system430 in two separate arrays containing the x and y wavefront gradientvalues obtained from image spot analysis of the Hartmann-Shack sensorimages, plus the x and y pupil center offsets from the nominal center ofthe Hartmann-Shack lenslet array, as measured by the pupil camera 451(FIG. ISA) image. Such information contains all the availableinformation on the wavefront error of the eye and is sufficient toreconstruct the wavefront or any portion of it. In such embodiments,there is no need to reprocess the Hartmann-Shack image more than once,and the data space required to store the gradient array is not large.For example, to accommodate an image of a pupil with an 8 mm diameter,an array of a 20×20 size (i.e., 400 elements) is often sufficient. Ascan be appreciated, in other embodiments, the wavefront data may bestored in a memory of the wavefront sensor system in a single array ormultiple arrays.

While the methods of many embodiments will generally be described withreference to sensing of an image 444, it should be understood that aseries of wavefront sensor data readings may be taken. For example, atime series of wavefront data readings may help to provide a moreaccurate overall determination of the ocular tissue aberrations. As theocular tissues can vary in shape over a period of time, a plurality oftemporally separated wavefront sensor measurements can avoid relying ona single snapshot of the optical characteristics as the basis for arefractive correcting procedure. Still further alternatives are alsoavailable, including taking wavefront sensor data of the eye with theeye in differing configurations, positions, and/or orientations. Forexample, a patient will often help maintain alignment of the eye withwavefront measurement system 430 by focusing on a fixation target, asdescribed in U.S. Pat. No. 6,004,313, the full disclosure of which isincorporated herein by reference. By varying a position of the fixationtarget as described in that reference, optical characteristics of theeye may be determined while the eye accommodates or adapts to image afield of view at a varying distance and/or angles.

The location of the optical axis of the eye may be verified by referenceto the data provided from the pupil camera 451. In many embodiments, thepupil camera 451 images the pupil 450 so as to determine a position ofthe pupil for registration of the wavefront sensor data relative to theoptical tissues.

An alternative embodiment of a wavefront measurement system isillustrated in FIG. 15B. FIG. 15B shows a system 1000 for measuringaberrations and corneal topography of an eye 100, in accordance withmany embodiments. The system 1000 comprises a topographer 1010, anaberrometer or wavefront analyzer 1020, and a processor 1410. Thetopographer 1010 comprises a structure 1100 having a principal surface1120 with an opening or aperture 1140 therein; a plurality of first (orperipheral) light sources 1200 provided on the principal surface 1120 ofthe structure 1100; a plurality of second, or central, light sources1300 (also sometimes referred to as “Helmholtz light sources”); and adetector, photo detector, or detector array 1400.

The wavefront analyzer 1020 of the system 1000 comprises a third lightsource 1500 providing a probe beam; a wavefront sensor 1550; and anoptical system 1700 disposed along a central axis 1002 passing throughthe opening or aperture 1140 of the structure 1100. The optical system1700 comprises a quarter wave plate 1710, a first beam splitter 1720, asecond beam splitter 1730, an optical element (e.g., a lens) 1740, athird beamsplitter 1760, and a structure including an aperture 1780.Beneficially, the third light source 1500 includes a lamp 1520, acollimating lens 1540, and light source polarizing beam splitter 1560.The lamp 1520 can be an SLD or a fiber-coupled source that optionallyincludes an optical coherence tomographer (OCT). Wavefront analyzer 1020further comprises a polarizing beam splitter 1620; an adjustabletelescope 1640 comprising a first optical element (e.g., lens) 1642 anda second optical element (e.g., lens) 1644 and a movable stage orplatform 1646; and a dynamic-range limiting aperture 1650 for limiting adynamic range of light provided to wavefront sensor 1550 so as topreclude data ambiguity. It will be appreciated by those of skill in theart that the lenses 1642, 1644, or any of the other lenses discussedherein, can be replaced or supplemented by another type of converging ordiverging optical element, such as a diffractive optical element.Beneficially, the system 1000 further comprises a fixation target system1800, comprising light source 1820 and lenses 1840, 1860, and 1880. Thestructure and use of the system 1000 of FIG. 15B are more fullydescribed in U.S. Patent Publication No. 2009/0161090 A1, the fulldisclosure of which is incorporated herein by reference. Anotherexemplary wavefront system is described in U.S. Pat. No. 6,550,917, thefull disclosure of which is incorporated herein by reference.

Although a wavefront elevation map may be created from optical gradientdata in any number of ways, wavefront elevation map creation by way offitting the gradient data to a combination of one or more Zernikepolynomials is one commonly used approach. Zernike polynomials representa particularly beneficial form of a mathematical series expansion formodeling the wavefront elevation map. FIG. 16 illustrates the shapes ofa subset of Zernike polynomials, which are a function of normalizedradius and angle for a given order and frequency. In many embodiments,Zernike polynomial sets including terms 0 through 6th order or 0 through10th order are used. The coefficients a_(n) for each Zernike polynomialZ_(n) may, for example, be determined using a standard least-squares fittechnique. In practice, the number of Zernike polynomial coefficientsused may be limited (for example, to about 28 coefficients).

Even Zernike Polynomials:Z _(n) ^(m)(ρ,θ)=R _(n) ^(m)(ρ)cos(mθ)Odd Zernike Polynomials:Z _(n) ^(−m)(ρ,θ)=R _(n) ^(m)(ρ)sin(mθ)where:m and n are nonnegative integers with n≥m,θ is the azimuthal angle in radians,ρ is the normalized radial distance, and

${R_{n}^{m}(\rho)} = {\sum\limits_{k = 0}^{{({n - m})}/2}{\frac{\left( {- 1} \right)^{k}{\left( {n - k} \right)!}}{{k!}{\left( {{\left( {n + m} \right)/2} - k} \right)!}{\left( {{\left( {n - m} \right)/2} - k} \right)!}}\rho^{n - {2k}}\mspace{14mu}\left( {{{if}\mspace{14mu} n} - {m\mspace{14mu}{is}\mspace{14mu}{even}}} \right)}}$  R_(n)^(m)(ρ) = 0  (if  n − m  is  odd)

Where an array of Zernike coefficients has been determined, thewavefront elevation map can be created. Scaling the Zernike polynomialsby their coefficients and summing the scaled Zernike polynomials allowsa wavefront elevation map to be calculated, and in some cases, may veryaccurately reconstruct a wavefront elevation map.

An additional benefit to wavefront elevation reconstruction by way ofZernike polynomials relates to the correspondence between certainZernike polynomial shapes and commonly known optical aberrations, suchas between Zernike polynomial for defocus (n=2, f=0) and nearsightednessor farsightedness, as well as the Zernike polynomial shapes forastigmatism (n=2, f=±2). The low-order aberrations of defocus andastigmatism account for a vast majority of the optical errors present ina typical eye.

However, high-order aberrations corresponding to high-order Zernikepolynomials do exist to a significant extent, and are associated withvision errors such as difficulty seeing at night, glare, halos,blurring, starburst patterns, double vision, or the like. Accordingly,improved vision correction may result by way of improved correction ofhigh-order aberrations. FIG. 17A illustrates a modal approximation of anexample wavefront surface.

Wavefront elevation maps can also be created for a wavefront measurementby using a zonal approximation. Exemplary approaches that can be used toapproximate a wavefront surface using a zonal approach are disclosed inU.S. Pat. No. 7,175,278, entitled “Wavefront Reconstruction UsingFourier Transformation and Direct Integration,” filed Jun. 20, 2003; andin U.S. Pat. No. 7,168,807, entitled “Interative Fourier Reconstructionfor Laser Surgery and Other Optical Application,” filed Jun. 17, 2004;the full disclosures of which are hereby incorporated herein byreference. Such zonal approximations can be used to more accuratelyapproximate wavefront surfaces having locally complex shapes as comparedto some modal approximation approaches (e.g., fitting 6^(th) orderZernike polynomials). FIG. 17B illustrates a zonal approximation of anexample wavefront surface, which includes locally complex shapes.

A zonal approximation can be processed to generate values for commonlyknown optical aberrations (e.g., such as discussed above). For example,the methods disclosed in U.S. Pat. No. 7,331,674, entitled “CalculatingZernike Coefficients from Fourier Coefficients,” filed Sep. 2, 2005, theentire disclosure of which is hereby incorporated herein by reference,can be used to calculate Zernike Coefficients for a modal approximationof the zonal approximation (e.g., terms for sphere, cylinder, coma,and/or other terms).

Optical Diagnosis and Correction Selection

FIG. 18 shows steps of a method 500 for diagnosing optical aberrationsof an eye, and formulating and assessing one or more candidate opticalcorrections, in accordance with many embodiments. The method can be usedto determine statistically-significant aberrations of the eye for one ormore viewing conditions. The identified statistically-significantaberrations can be quantified and used to formulate one or morecandidate corrections, the performance of which can be assessed relativeto the aberrations of the eye for one or more viewing conditions.

In step 502, a sequence of aberration measurements is obtained. In manyembodiments, the measurement sequence is obtained by using a wavefrontsystem such as described above. The sequence of measurements can beobtained during a single examination period, and can also be obtainedover two or more examination periods. In many embodiments, the viewingconditions are varied and/or changed while the sequence of measurementsis obtained. For example, a plurality of viewing distances and/orillumination levels can be used as described in U.S. Pat. No. 7,513,620,the full disclosure of which is hereby incorporated herein by reference.Different portions of the sequence of measurements can be dedicated todifferent viewing conditions. And each portion can include a sufficientnumber of measurements to establish a sufficient basis from which todetermine a suitable number of component aberrations for the viewingcondition, which can include both low-order aberrations and a suitablenumber of high-order aberrations for the desired accuracy of the opticaldiagnosis. As will be described in more detail below, varying theviewing conditions enables the determination of the aberrations of theeye for the varied viewing conditions. And the determined aberrationsfor the varied viewing conditions can be used to formulate/assess anoptical correction for the eye.

For example, FIG. 19A illustrates a sequence of accommodationmeasurements (via measured refraction) and pupil radius measurements ofa young eye. The measurement sequence begins with the eye viewing a fartarget. The viewing target is then changed to be a near target, therebycausing the eye to accommodate as illustrated by the change in themeasured refraction. Finally, the viewing target is then changed back tobe a far target, thereby resulting in the illustrated change in themeasured refraction. During the measurement sequence, the pupil radiusis also measured.

Steps 504, 506, 508 are used to register the aberration measurementswith a fixed reference of the eye. This registration ensures that duringsubsequent processing the individual aberration measurements can be morereadily compared due to the common reference frame. In step 504, arelationship for the eye between pupil size and pupil location isdetermined. The pupil size/location relationship (e.g., as illustratedin FIG. 12 and FIG. 14) can be determined as described above. In step506, each measurement of the sequence of aberration measurements isprocessed to determine the pupil size for the measurement. The pupilsize for the measurement (e.g., as illustrated in FIG. 7) can bedetermined as described above. Once the pupil size for the measurementis determined, the pupil location for the measurement can be determinedusing the above-described relationship. And the aberration measurementcan be registered using the determined pupil location.

In step 510, component aberrations are determined for each measurementof the sequence of measurements. In many embodiments, each measurementof the sequence of measurements is used to generate a wavefrontelevation map for the measurement. As described above, the componentaberrations can be determined by fitting a combination of one or moreZernike polynomials to the measurement gradient data. As a result,sequences of Zernike polynomial coefficients corresponding to individualcomponent aberrations of the sequence of measured aberrations aregenerated. The variation of any particular Zernike polynomial during thesequence of measurements (or portion of the sequence) can then beobserved and/or quantified.

In step 512, any outlier measurements can be identified so that they canbe excluded from subsequent processing. For example, FIG. 19Billustrates outlier accommodation measurements caused by blinks andpartial blinks. Such blinks and partial blinks interfere with one ormore wavefront measurements, as illustrated by the abrupt change in themeasured pupil radius and the measured refraction, thereby producingoutlier measurements. By excluding such outlier measurements, aqualified sequence of accommodation measurements can be obtained such asillustrated in FIG. 19C.

Data qualification for measurements (e.g., accommodation measurements,aberration measurements) can be based on physically reasonable limits.For example, qualified data can be limited to measurements in which thepupil center is well within the sensor field of view. As pupil radii areseldom less than 1 mm, blinks can be identified by checking the sequenceof pupil radius measurements for pupil radii of less than apredetermined value (e.g., less than 0.5 mm). Partial blinks and fieldof view errors can be identified by checking the magnitude of the rateof change of the pupil radii for rates of change greater than apredetermined rate (e.g., greater than 3 mm/sec). As pupil radii willtypically change by more than 0.5 mm when accommodating, a pupil radiusfor a near viewing condition and a pupil radius for a far viewingcondition can be required to differ by more than a predetermined amount(e.g., 0.5 mm). Some outlier sphere equivalent refraction (SEQ) can beidentified due to being outside a predetermined range such as areasonably expected range (e.g., less than −15D or greater than ±15D).Some outlier SEQ measurements can be identified by checking to see ifthe magnitude of the rate of change of SEQ is greater than apredetermined rate (e.g., greater than 25D per second). Proper fixationon a far viewing target can be checked by comparing the resulting farSEQ to the manifest refraction of the eye. If the magnitude of thedifference between the far SEQ and the manifest refraction is greaterthan a predetermined value (e.g., greater than 1.5D), the far target mayhave been out of focus to the subject. Proper fixation on a near viewingtarget can be checked by comparing the resulting near SEQ to themanifest refraction of the eye minus the stimulus. If the magnitude ofthe difference between the near SEQ and the manifest refraction minusthe stimulus is greater than a predetermined value (e.g., greater than2D), the near target may have been out of focus to the subject.

Data qualification for measurements can also be based upon detecting anoutlier measurement(s) that has a transitory high-order aberration(s) byidentifying an aberration measurement having an elevated Wavefront FitError (WFFE) as compared to other aberration measurements of thesequence of measurements. As transitory higher-order aberrations may notbe as accurately approximated by a modal approximation approach, and asa zonal approximation approach may more accurately approximate suchtransitory higher-order aberrations, an elevated difference between amodal approximation and a zonal approximation for the same measurementmay be indicative of the presence of such a transitory higher-orderaberration.

A gradient fit error (β_(fit)) can be scaled by the measurement size atthe eye (d) to approximate the WFFE.WFFE≈β_(fit) d

The gradient fit error (β_(fit)) can be calculated from a wavefrontmeasurement and a modal reconstruction of the wavefront measurement. Ina modal reconstruction of the wavefront measurement, the wavefrontsurface is expressed in terms of a polynomial expansion (e.g., Zernikepolynomials, Taylor polynomials).

${w\left( {x,y} \right)} = {\sum\limits_{m = 1}^{M}{C_{m}{P_{m}\left( {x,y} \right)}}}$

The measured slopes are fit to the derivatives of the basis set.

$\left( \frac{\partial w}{\partial x} \right)_{k} = {{\sum\limits_{m = 2}^{M}{C_{m}\frac{\partial P_{m}}{\partial x}\mspace{45mu}\left( \frac{\partial w}{\partial y} \right)_{k}}} = {\sum\limits_{m = 2}^{M}{C_{m}\frac{\partial P_{m}}{\partial y}}}}$

The gradient fit error (β_(fit)) can then be calculated using theaberration measurement and the modal reconstruction.

$\mspace{20mu}{\beta_{fit}^{2} = {{\sum\limits_{k}\left( {\beta_{k}^{x} - {\sum\limits_{m = 2}^{M}{C_{m}\frac{\partial P_{m}}{\partial x}}}} \right)^{2}} + {\sum\limits_{k}\left( {\beta_{k}^{y} - {\sum\limits_{m = 2}^{M}{C_{m}\frac{\partial P_{m}}{\partial y}}}} \right)^{2}}}}$$\beta_{fit}^{2} = {{\frac{1}{N}{\sum\limits_{k}\left( {\beta_{k}^{x} - {\sum\limits_{m = 2}^{M}{C_{m}\frac{\partial{P_{m}\left( {x_{k},y_{k}} \right)}}{\partial x}}}} \right)^{2}}} + {\frac{1}{N}{\sum\limits_{k}\left( {\beta_{k}^{y} - {\sum\limits_{m = 2}^{M}{C_{m}\frac{\partial{P_{m}\left( {x_{k},y_{k}} \right)}}{\partial y}}}} \right)^{2}}}}$Wherein β_(k) ^(x) and β_(k) ^(y) are measured slope values of theaberration measurement.

While a non-outlier aberration measurement may produce modal and zonalapproximations that correlate well, an outlier aberration measurementmay produce modal and zonal approximations that deviate significantly.For example, FIG. 20A shows a difference between a zonal approximationof a wavefront surface and a modal approximation of a wavefront surfacefor a typical wavefront measurement that is closely approximated by amodal approximation. In the wavefront measurement of FIG. 20A, the totalzonal root mean square (RMS) error is 1.853 μm, the total modal RMS is1.842 μm, the residual zonal-modal RMS error is 0.058 μm, and the WFFEis 0.0838 μm. Likewise, FIG. 20B is a slope residual map showing lowresidual fit error between a modal approximation of the wavefrontsurface of the wavefront measurement of FIG. 20A. In contrast, FIG. 20Cshows a difference between a zonal approximation of a wavefront surfaceand a 6^(th) order modal approximation of a wavefront surface for awavefront measurement influenced by a tear film. In the wavefrontmeasurement of FIG. 20C, the total zonal RMS error is 1.276 μm, thetotal modal RMS is 1.220 μm, the residual zonal-modal error is 0.338 μm,and the WFFE is 0.551 μm.

Outliner aberration measurements can also be identified by statisticallyevaluating one or more sequences of component aberrations (e.g., one ormore sequences of Zernike polynomial coefficients corresponding toindividual component aberrations of the sequence of measuredaberrations) using known statistical methods. For example, a blink maybe identified by detecting a statistically-significant variation in asequence of Zernike coefficients corresponding to a stable lower-orderaberration.

In step 514, one or more post-blink measurements can be identified forpossible exclusion from subsequence processing. A post-blink measurementis a measurement taken immediately following a blink of an eye (e.g.,less than one-quarter second following the end of a blink). Post-blinkmeasurements may exhibit transitory aberrations arising from the blink.For example, blink induced transitory changes in the tear film mayinduce such transitory aberrations. As such, exclusion of post-blinkmeasurements from subsequent processing can be used to prevent suchtransitory aberrations from influencing the results of the opticaldiagnosis.

In step 516, statistically-significant component aberrations aredetermined. Each sequence of component aberrations can be analyzed usingknown statistical methods to determine whether that particular componentaberration is statistically significant. Often, low-order componentaberrations will be statistically significant. And the question comesdown to whether particular high-order aberrations are statisticallysignificant. As such, the analysis can focus on selected high-orderaberrations, for example, third-order through eighth-order aberrations.For example, FIG. 21 illustrates an exemplary sequence of values for aneighth-order component aberration (Zernike 40). Astatistically-significant component aberration exhibits relativestability over a sequence of measurements for a particular viewingcondition.

In step 518, the statistically-significant component aberrationsidentified as describe above are quantified. As illustrated in FIG. 21,a component aberration may exhibit some level of variability over timeand yet be relatively stable for the viewing condition involved. Forexample, the sequence of determined coefficients for the Zernike 40aberration shown in FIG. 21 can be processed to generate a singlerepresentative number for the aberration component (e.g., by averagingthe coefficients of non-excluded measurements for a particular viewingcondition, by using a least-squares-fit method).

In step 520, one or more candidate optical corrections are formulatedand assessed relative to one or more viewing conditions. A candidateoptical correction can be formulated in a variety of ways. One approachinvolves formulating an optical correction that partially or fullyaddresses one or more, and possibly all, of the statistically relevantaberrations of the eye that were measured, identified, and quantified asdescribed above. Such an optical correction can be assembled byselecting coefficients for component optical corrections that correspondto the statistically-significant component aberrations. For example, ifa particular component aberration varies from a first value to a secondvalue over a range of viewing conditions, a value intermediate to thefirst and second values can be selected for that particular correctioncomponent of the candidate optical correction. Other approaches forselecting a candidate optical correction can be used. For example, apreviously identified defect-correcting prescription can be simplyprovided as a starting point. The defect-correcting prescription canalso be identified using methods described in numerous patents, patentpublications, and patent applications assigned to Advanced MedicalOptics, Inc., including, for example, U.S. Pat. Nos. 6,280,435;6,663,619; 7,261,412; 7,293,873; 7,320,517; 7,387,387; 7,413,566;7,434,936; 7,475,986; 7,478,907; and U.S. Pat. Publication Nos.2004/0054356 A1; US 2005/0261752 A1; 2008/0291395 A1; 2009/0000628 A1;and 2009/0036981 A1; the entire disclosures of which are herebyincorporated by reference herein.

A candidate optical correction can also be formulated corresponding to aselected group of Zernike coefficients suitable for the correctivetechnique to be employed (e.g., corrective glasses, laser-eye surgery,contacts, etc.). For example, FIG. 16 shows a group of coefficients 522that includes a particular symmetrical selection of Zernike polynomialscorresponding to component that may be suitable for a particularcorrection. With corrective techniques involving relative movementbetween the eye and the corrective means (e.g., glasses, contacts), agroup of coefficients targeting mostly lower-order aberrations may besuitable. For laser eye surgery, the addition of more higher-orderaberrations may be suitable.

The candidate optical correction can then be assessed relative to one ormore viewing conditions. For example, a merit function can be used toassess the candidate correction.

$\begin{matrix}{{MF} = {\sum\limits_{k}{I_{k}{\sum\limits_{pupil}\left\lbrack {{W_{k}\left( {x,y} \right)} - {R\left( {x,y} \right)}} \right\rbrack^{2}}}}} & {{Equation}\mspace{14mu}(1)}\end{matrix}$Where:

-   -   k indicates a particular measurement of the sequence of        aberration measurements;    -   I_(k) is a factor that can be used weight particular        measurements (e.g., can be zero to    -   eliminate outlier measurements, post-blink measurements, etc.)    -   W_(k)(x,y) is a particular wavefront measurement; and    -   R(x,y) is the candidate correction as defined by equation (2)        below        R(x,y)=S(x ² +y ²)/2+C[(x cos ϕ)²+(y sin ϕ)²]/2  Equation (2)

Equation (1) sums the differences between each wavefront measurement andthe candidate correction over the pupil to limit the assessment to theactive part of the eye for that measurement. The relative performance ofcandidate corrections can be compared by using Equation (1) with a fixedset of measurements used for W_(k)(x,y) for each candidate correctionassessed.

Variations of Equation (1) can also be used to assess one or morecandidate optical corrections. For example, instead of using actualaberration measurements for W_(k)(x,y), a combination of thestatistically-significant component aberrations for particular viewingconditions can be used. Additionally, I_(k) can be used to weight aparticular viewing condition to reflect a level of importance associatedwith the viewing condition. For example, a 0.4 factor can be used toweight a daytime viewing condition, a 0.4 factor can be used to weight a“work” viewing condition, and a 0.2 factor can be used to weight a“sport” viewing condition. Thus, one or more candidate corrections canbe assessed (and compared) relative to any selected number of viewingconditions. And the viewing conditions can be weighted according torelative importance during the assessment.

The above-described approaches can also be used to create opticalcorrections customized for an activity. For example, a correction can bedetermined for use at night. Likewise, a correction can be determinedfor use during the day. The daytime and nighttime corrections can beincorporated into various means for applying a correction including, forexample, spectacles and/or contact lenses.

The above-described approaches can also be customized for laser-assistedin situ keratomileusis (LASIK) eye surgery and Photorefractivekeratectomy (PRK) eye surgery. For example, known error terms can beincluded (e.g., healing response, laser alignment to eye, trackingerror, etc.).

Configuring Contact Lenses

FIG. 22 shows steps of a method 600 for configuring a contact lens, inaccordance with many embodiments. The method can be used to determinewhich high-order corrections to incorporate into the contact lens.

In step 602, a corrective prescription for the eye is obtained. Forexample, the corrective prescription can be obtained using any of theapproaches described or referenced above with respect to the candidateoptical correction.

In step 604, a sequence of positions and orientations of a contact(disposed in an eye) relative to the eye are measured. For eachmeasurement, the position and orientation of the eye can be tracked asdescribed above. Reference marks can be added to the contact and theposition and orientation of the reference marks tracked relative to theeye so as to provide both relative position and relative orientationmeasurements between the contact and the eye.

The sequence of relative positions and orientations are analyzed in step606 to determine statistical dispersions for the sequence of relativepositions and orientations. For example, a mean relative position and amean relative orientation can be determined. And the standard deviationfor both the relative positions and the relative orientations can bedetermined.

In step 608, one or more candidate corrections are formulated. In manyembodiments, which high-order corrections to include into a candidatecorrection are determined in response to the amount of statisticaldispersion observed in the relative positions and/or the relativeorientations. For example, where the relative positions vary by morethan 1 mm, third-order and higher corrections can be excluded from thecandidate correction (e.g., only first and second-order corrections areincluded). And where the relative positions vary by between 0.5 to 1.0mm, for example, fourth-order and higher corrections can be excluded.And where the relative positions vary less than 0.5 mm, for example,seventh-order and higher corrections can be excluded. Other approachescan be used for formulating a candidate correction, for example, any ofthe above-described or references approaches.

In step 610, the performance of the one or more candidate corrections isassessed over one or more relative positions and/or relativeorientations based on the observed statistical dispersion of therelative positions and/or the relative orientations. Equation (1) setforth above can be used to perform this assessment by inducing arelative shift in position and/or orientation of W_(k)(x,y) or R(x,y)(preferably R(x,y) to reduce the amount of computations required) via asuitable imposed translation or rotation for each relative positionand/or relative orientation assessed.

Step 612 can be used to assess the performance of the one or morecandidate corrections relative to one or more additional viewingconditions. Step 612 can be accomplished using the approach of step 610described above, but in which the W_(k)(x,y) is selected to reflect theviewing condition being assessed.

The method 600 can be adapted for use with other types of visioncorrections. For example, the direction that an eye looks through aspectacle lens varies. Such a variation can be tracked and used toconfigure the spectacle lens so as to best reflect the observedvariation.

While exemplary embodiments have been described herein in some detail,for clarity of understanding and by way of example, a variety ofadaptations, changes, and modifications will be clear to those of skillin the art. For example, a variety of wavefront sensor systems from avariety of alternative suppliers may be employed. Thus, while theinvention is susceptible to various modifications and alternativeconstructions, certain illustrated embodiments thereof are shown in thedrawings and have been described above in detail. It should beunderstood, however, that there is no intention to limit the inventionto the specific form or forms disclosed, but on the contrary, theintention is to cover all modifications, alternative constructions, andequivalents falling within the spirit and scope of the invention, asdefined in the appended claims.

The use of the terms “a” and “an” and “the” and similar referents in thecontext of describing the invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. The terms “comprising,” “having,” “including,” and “containing”are to be construed as open-ended terms (i.e., meaning “including, butnot limited to,”) unless otherwise noted. The term “connected” is to beconstrued as partly or wholly contained within, attached to, or joinedtogether, even if there is something intervening. Recitation of rangesof values herein are merely intended to serve as a shorthand method ofreferring individually to each separate value falling within the range,unless otherwise indicated herein, and each separate value isincorporated into the specification as if it were individually recitedherein. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein, is intended merely to betterilluminate embodiments of the invention and does not pose a limitationon the scope of the invention unless otherwise claimed. No language inthe specification should be construed as indicating any non-claimedelement as essential to the practice of the invention.

Preferred embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention.Variations of those preferred embodiments may become apparent to thoseof ordinary skill in the art upon reading the foregoing description. Theinventors expect skilled artisans to employ such variations asappropriate, and the inventors intend for the invention to be practicedotherwise than as specifically described herein. Accordingly, thisinvention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference to the sameextent as if each reference were individually and specifically indicatedto be incorporated by reference and were set forth in its entiretyherein.

What is claimed is:
 1. A method, comprising: employing a wavefrontmeasurement device to obtain a time sequence of aberration measurementsof an eye, wherein each aberration measurement in the time sequence isassociated with a time parameter; identifying an outlier aberrationmeasurement of the time sequence of aberration measurements of the eyebased on an analysis of a change of at least one measured property ofthe eye with time; excluding the outlier aberration measurement from thesequence of aberration measurements of the eye to produce a qualifiedtime sequence of aberration measurements for the eye; and formulating anoptical correction for the eye in response to the qualified timesequence of aberration measurements of the eye.
 2. The method of claim1, further comprising registering at least one of the time sequence ofaberration measurements or the qualified time sequence of aberrationmeasurements by using at least one of a location of the eye or anorientation of the eye.
 3. The method of claim 1, wherein the step ofidentifying an outlier aberration measurement comprises: determining atime sequence of coefficients corresponding to a component aberration ofthe eye in response to the sequence of aberration measurements; andprocessing the time sequence of coefficients to determine whether thecomponent aberration is statistically significant.
 4. The method ofclaim 1, wherein the step of identifying an outlier aberrationmeasurement comprises one of: identifying a sphere equivalent refraction(SEQ) of the eye that is outside a predetermined range, identifying arate of change of SEQ of the eye that is greater than a predeterminedrate, identifying a SEQ of the eye for a measurement corresponding toviewing a far viewing target that differs from a manifest refraction ofthe eye by more than a predetermined value, and identifying a SEQ of theeye for a measurement corresponding to viewing a near viewing targetthat differs from a manifest refraction of the eye minus a stimuluscorresponding to the near viewing target by more than a predeterminedvalue.
 5. The method of claim 1, wherein the step of identifying anoutlier aberration measurement comprises identifying a measurement ofthe time sequence having a first wavefront fit error (WFFE) that exceedsa second WFFE of a second measurement of the time sequence by more thana predetermined amount.
 6. The method of claim 1, wherein the eye issubjected to a plurality of viewing conditions comprising a firstviewing condition and a second viewing condition, wherein a change fromthe first to the second viewing condition induces an accommodation ofthe eye, wherein the first viewing condition comprises viewing a fartarget and the second viewing condition comprises viewing a near target;and wherein the step of identifying an outlier aberration measurementcomprises identifying pupil radii, when the viewing condition changesfrom the first to the second viewing condition, that differ by less thana predetermined amount.
 7. The method of claim 1, further comprisingdetermining statistically-significant component aberrations of the eyefor a plurality of the viewing conditions.
 8. The method of claim 7,further comprising determining a performance of a candidate opticalcorrection for the eye over a plurality of the viewing conditions byusing a merit function that assesses the candidate optical correctionrelative to the plurality of the viewing conditions.
 9. The method ofclaim 8, wherein the merit function comprises at least one factor toaccount for a relative importance of at least one of the plurality ofviewing conditions.
 10. The method of claim 8, wherein the step ofdetermining a performance of a candidate optical correction for the eyecomprises assessing the candidate optical correction relative to theplurality of viewing conditions over a portion of the eye correspondingto a pupil size of the eye and a pupil location of the eye for theviewing condition.
 11. The method of claim 1, further comprising:determining a performance of each of a plurality of candidate opticalcorrections for the eye over each of a plurality of viewing conditions;and determining a prescriptive optical correction for the eye inresponse to the determined performances for the candidate opticalcorrections.
 12. The method of claim 1, wherein identifying an outlieraberration measurement of the time sequence of aberration measurementsof the eye based on the analysis of the change of the at least onemeasured property of the eye with time includes identifying a post-blinkaberration measurement that follows a blink of the eye by less than apredetermined amount of time.
 13. The method of claim 12, includesidentifying the blink by detecting in the time sequence of aberrationmeasurements of the eye a statistically-significant variation in asequence of Zernike coefficients corresponding to a stable lower-orderaberration of the eye.
 14. The method of claim 1, wherein eachaberration measurement of the eye measures a combined aberration of theeye and wherein a plurality of component aberrations approximate thecombined aberration, the method further comprising: subjecting the eyeto a plurality of different viewing conditions during the sequence ofaberration measurements; and determining an effect of the differentviewing conditions on the component aberrations.
 15. The method of claim14, wherein the optical correction for the eye is selected based on howthe component aberrations vary with the different viewing conditions.16. The method of claim 15, wherein the optical correction for the eyecomprises a plurality of component optical corrections, the methodfurther comprising selecting coefficients for the component opticalcorrections that correspond to statistically-significant componentaberrations among the component aberrations.
 17. The method of claim 1,further comprising determining statistically-significant componentaberrations of the eye for a plurality of the viewing conditionsincluding at least a first viewing condition of viewing a viewing targetat a first distance from the eye and a second viewing condition ofviewing the viewing target at a second distance from the eye, whereinthe second distance is greater than the first distance.
 18. The methodof claim 17, further comprising determining a performance of a candidateoptical correction for the eye over a plurality of the viewingconditions by using a merit function that assesses the candidate opticalcorrection relative to the plurality of the viewing conditions.
 19. Themethod of claim 18, wherein the merit function comprises at least onefactor to account for a relative importance of at least one of theplurality of viewing conditions.
 20. The method of claim 18, wherein thestep of determining the performance of the candidate optical correctionfor the eye comprises assessing the candidate optical correctionrelative to the plurality of viewing conditions over a portion of theeye corresponding to a pupil size of the eye and a pupil location of theeye for the viewing condition.